: Dr. Vijendra Singh, a neuroimmunologist, is working on the developmental aspect of the immune: system and nervous system and itís relationships to autism. He firmly believes that up to 80% (and: possibly all) cases of autism are caused by an abnormal immune reaction, commonly known as: autoimmunity. Specifically, he is exploring the role of autoimmune factors (for example, viruses,: autoantibodies, T cells, cytokines, ect.) because they serve as the prime targets of therapy with: immune modulating drugs, he said.

: Dr. Singh thinks that autism is a complex disorder of a very complicated interaction between the: nervous system and the immune system. He postulated a "Neuroautoimmunity Model of Autism": which he recently discussed at two recent meetings: First, the Biomedical Treatments for Autism: and PDD Conference held in Orlando, Florida (May, 1999); and secondly, the Neuro-Immune: Dysfunction Syndromes (NIDS) Conference held in Bethesda, Maryland (June, 1999). Briefly, he: hypothesized that an autoimmune reaction to brain structures, in particular myelin sheath, plays a: critical role in causing neurological impairments of patients with autism. He thinks that an immune: damage to developing myelin (after a natural infection or vaccination) causes "nicks" or small: changes in the myelin sheath, which ultimately leads to life-long problems of higher mental functions: such as the skills for learning, memory, communication, social interaction, etc.

: Dr. Singh believes that autoimmunity has a strong prospect for treating patients with autism. He: said that the lessons learned from other autoimmune diseases should also apply to autism. Because: of autoimmunity involvement, he emphasizes the need to focus on immune therapies and urge: doctors to pay attention to this line of research. Consequently, he says, there is a strong potential: for restoring brain functions in autistic patients, including children as well as adults. With this goal in: mind, Dr. Singh is committed to finding a cause and cure for autism.

: The following hypothesis, based on the work of Ellen Bolte, is at the heart of the research that is: being done at the Wadsworth Anaerobic Bacteriology Laboratory, West Los Angeles, CA.: Hypothesis: A bacterial toxin, genetically related to the clostridial neurotoxins, causes the: behavioral abnormalities associated with autism (via severe disruption of neurotransmitter release): in a narrowly defined subset of children.

: Many autistic children have severe gastrointestinal problems. Chronic diarrhea or loose stools is: commonly reported from parents of autistic children. The research team at the Wadsworth: Laboratory speculate that broad-spectrum antibiotics (frequently used to treat ear infections) may: cause significant disruption of the protective intestinal tract flora and that this disruption may allow: for colonization by one or more neurotoxin-producing bacteria. The neurotoxin produced in the: intestinal tract then ascends to the central nervous system and creates an on-going state of: neurotransmitter disruption.

: In an initial study, eleven children were treated with a minimally absorbed oral antibiotic. Nine of: the eleven children showed improvement during therapy. One child had no change and the other: possibly became worse. Pre-treatment stools were found to have numerous unidentifiable: Clostridium species. No Clostridium were found in the stools from the "on-therapy" specimens of: the children that benefitted from the treatment. Interestingly, the "on-therapy" stool specimen from: the child who appeared to deteriorate during treatment contained multiple Clostridium species.: The improvements in these children was short term and did not continue after treatment was: terminated. However, the fact that there was improvement in such a short time period, shows that: it is highly probable that a bacterial infection causes or worsens at least some (if not all) of the: autistic symptoms in these children.

: The research team is working to identify the specific offending organism(s) involved, which causes: the autistic symptoms. Upon isolation of the organism(s), the team will then be able to determine: an effective treatment for the elimination of this "bug" from the gut. This work looks extremely: promising. The BHARE Foundation feels it is simply a matter of time before this research yields: discoveries that will directly benefit our children.

: Andrew Wakefield, leads a team of eight medical and scientific researchers, investigating a: meta-hypothesis; that a complex relationship between a genetic predisposition, and early: environmental exposures results in immune derangement and metabolic dysfunction. This primary: sequence of events takes place in the gut which then triggers an autistic disorder.

: Andrew Wakefield's particular interest is in children who develop normally and then manifest an: autistic disorder combined with gastrointestinal symptoms. A few years ago such cases were very: rare. More recently there is evidence of a significant increase in their prevalence. Wakefield and: colleagues have dubbed this syndrome 'autistic enterocolitis'. Examples of three current: programmes receiving assistance from the BHARE Foundation are mentioned below.

: Histopathologist Dr Andrew Anthony, is investigating the gut pathology of autistic enterocolitis,: and assessing possible non-invasive tests of specific features of the gut disorder seen in autistic: enterocolitis. At present most children referred to Andrew Wakefield's colleagues require: ileo-colonoscopy, an invasive procedure for which there is a lengthy wait. Children with autistic: enterocolitis display a remarkable uniformity in their endoscopic and histological symptoms. At: present 98% of affected children show a distinctive pattern of swollen lymph glands at the end of: the small bowel and 88% have inflammation of the large bowel.

: Immunologist Dr Paul Ashwood, is investigating specific immunologic features of autistic: enterocolitis. These concern the apparent dysregulation of certain helper T cells, thus impairing: their ability to stimulate a full cytotoxic response from particular classes of cytolytic T cells.: Epidemiologist Dr Scott Montgomery, is engaged in population-based studies to confirm the: reported temporal trends in the epidemiology of autism. These studies will be used to explore: explanations for the apparent increase in the incidence of autistic spectrum disorders and the: reported changes in phenotype, such as an increase in the number of children with regressive: autism. The work will include an investigation of the role of potential risk factors for autism,: specifically the combination of environmental exposures resulting in disease among susceptible: individuals. Identification of markers of susceptibility in both parents and the children themselves: will also assist in defining the 'at-risk' group for specific exposures. Other current and planned: investigations, include studies in virology, molecular biology, genetics and two trials of potential: therapies.

: For further information please contact Andrew Wakefield directly, at the address below or by: e-mail via robertsawyer@aol.com (Robert Sawyer handles all general enquiries and research: funding for Andrew Wakefield and his research team).